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Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6-23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.
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Encéfalo , Transcriptoma , Humanos , Neurônios Dopaminérgicos , Neurônios GABAérgicos , Mesencéfalo , Neocórtex , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismoRESUMO
BACKGROUND AND AIMS: The innate-like mucosa-associated invariant T (MAIT) cells are enriched in human liver and have been linked to human HCC. However, their contributions to the progression of HCC are controversial due to the heterogeneity of MAIT cells, and new MAIT cell subsets remain to be explored. APPROACH AND RESULTS: Combining single cell RNA sequencing (scRNA-seq) and flow cytometry analysis, we performed phenotypic and functional studies and found that FOXP3 + CXCR3 + MAIT cells in HCC patients were regulatory MAIT cells (MAITregs) with high immunosuppressive potential. These MAITregs were induced under Treg-inducing condition and predominantly from FOXP3 - CXCR3 + MAIT cells, which displayed mild Treg-related features and represented a pre-MAITreg reservoir. In addition, the induction and function of MAITregs were promoted by ß1 adrenergic receptor signaling in pre-MAITregs and MAITregs, respectively. In HCC patients, high proportion of the intratumoral MAITregs inhibited antitumor immune responses and was associated with poor clinical outcomes. CONCLUSIONS: Together, we reveal an immunosuppressive subset of MAIT cells in HCC patients that contributes to HCC progression, and propose a control through neuroimmune crosstalk.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Células T Invariantes Associadas à Mucosa , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Mucosa , Fatores de Transcrição Forkhead , Receptores AdrenérgicosRESUMO
BACKGROUND: In Asian patients with severe ptosis,the use of conjoint fascia sheath (CFS) suspension or levator aponeurosis fascia complex shortening surgery can correct the ptosis. During these surgery, a significant amount of levator aponeurosis fascia shortening is performed, which often leads to serious complications such as conjunctival prolapse.This study compares two surgical approaches for correcting severe blepharoptosis:Conjoint fascial sheath (CFS) + levator aponeurosis and muller's muscle complex (LM complex) suspension and conjoint fascial sheath (CFS) + LM complex+conjunctival suspension.The postoperative efficacy and the incidence of complications such as conjunctival prolapse are investigated for both procedures. METHODS: This study retrospectively analyzed 70 patients (77eyes) with severe blepharoptosis from January 2019 to December 2021. The patients were divided into the experimental group (34 cases, 38 eyes) and the control group (36 cases, 39 eyes). The experimental group was treated with CFS+LM complex + conjunctival suspension, and the control group was treated with CFS+LM complex suspension.The curative effect of blepharoptosis, the incidence of complications such as conjunctival prolapse and patient satisfaction were compared between the two different surgical methods. RESULTS: There was no significant difference in the correction effective rate between the experimental group (84.21%) and the control group (82.05%) (P > 0.05). There was no significant difference in the total incidence of complications between the experimental group (23.68%) and the control group (38.46%) (P > 0.05), but in the complication of conjunctival prolapse, the incidence of conjunctival prolapse in the experimental group was significantly lower than that in the control group. The difference was statistically significant (P < 0.05). In the survey of patient satisfaction rate, the satisfaction rate of the experimental group was significantly higher than that of the control group,which was statistically significant (P < 0.05). CONCLUSIONS: Compared to CFS+LM complex suspension surgery, the CFS+LM complex + conjunctival suspension has a definite effect in preventing postoperative conjunctival prolapse .The procedure has a high feasibility, good corrective effect, and improves patient satisfaction after surgery.
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Blefaroplastia , Blefaroptose , Humanos , Blefaroptose/cirurgia , Blefaroplastia/métodos , Estudos Retrospectivos , Prolapso , Pálpebras/cirurgia , Músculos Oculomotores/cirurgia , Resultado do TratamentoRESUMO
Thioethers are critical in the fields of pharmaceuticals and organic synthesis, but most of the methods for synthesis alkyl thioethers employ foul-smelling thiols as starting materials or generate them as by-products. Additionally, most thiols are air-sensitive and are easily oxidized to produce disulfides under atmospheric conditions; thus, a novel method for synthesizing thioethers is necessary. This paper reports a simple, effective, green method for synthesizing dialkyl or alkyl aryl thioether derivatives using odorless, stable, low-cost ROCS2K as a thiol surrogate. This transformation offers a broad substrate scope and good functional group tolerance with excellent selectivity. The reaction likely proceeds via xanthate intermediates, which can be readily generated via the nucleophilic substitution of alkyl halides or aryl halides with ROCS2K under transition-metal-free and base-free conditions.
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BACKGROUND: EEG monitoring techniques are receiving increasing clinical attention as a common method of reflecting the depth of sedation in the perioperative period. The influence of depth of sedation indices such as the bispectral index (BIS) generated by the processed electroencephalogram (pEEG) machine to guide the management of anesthetic depth of sedation on postoperative outcome remains controversial. This research was designed to decide whether an anesthetic agent exposure determined by raw electroencephalogram (rEEG) can influence anesthetic management and cause different EEG patterns and affect various patient outcomes. METHODS: A total of 141 participants aged ≥ 60 years undergoing abdominal major surgery were randomized to rEEG-guided anesthesia or routine care group. The rEEG-guided anesthesia group had propofol titrated to keep the rEEG waveform at the C-D sedation depth during surgery, while in the routine care group the anesthetist was masked to the patient's rEEG waveform and guided the anesthetic management only through clinical experience. The primary outcome was the presence of postoperative complications, the secondary outcomes included intraoperative anesthetic management and different EEG patterns. RESULTS: There were no statistically significant differences in the occurrence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. Further EEG analysis revealed that lower frontal alpha power was significantly associated with a higher incidence of POD, and that rEEG-guidance not only reduced the duration of deeper anesthesia in patients with lower frontal alpha power, but also allowed patients with higher frontal alpha power to receive deeper and more appropriate depths of anesthesia than in the routine care group. CONCLUSIONS: In elderly patients undergoing major abdominal surgery, rEEG-guided anesthesia did not reduce the incidence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. rEEG-guided anesthesia management reduced the duration of intraoperative BS in patients and the duration of over-deep sedation in patients with lower frontal alpha waves under anesthesia, and there was a strong association between lower frontal alpha power under anesthesia and the development of POD. rEEG-guided anesthesia may improve the prognosis of patients with vulnerable brains by improving the early identification of frail elderly patients and providing them with a more effective individualized anesthetic managements.
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Anestesia , Anestésicos , Gastroenteropatias , Propofol , Idoso , Humanos , Eletroencefalografia/métodos , Anestesia Geral/métodosRESUMO
Sewage sludge (SS) has been extensively used as an alternative fertilizer in forest plantations, which are beneficial in supplying timbers and mitigating climate change. However, whether the extra nitrogen (N) applied by SS would enhance the soil nitrous oxide (N2O) emission, an important greenhouse gas, in forest plantations have not been well understood. The objective of this study is to evaluate the ecological effects of SS application on soils, by investigating the soil N2O emission and the toxicity of the potentially toxic elements (PTEs) in soil. A field fertilization experiment was conducted in Eucalyptus plantations with four fertilization rates (0 kg m-2, 1.5 kg m-2, 3.0 kg m-2, and 4.5 kg m-2). The soil N2O emissions were monitored at a soil depth of 0-10 cm using static chamber method, soil chemical properties, and PTEs were determined at soil depths of 0-10 cm, 10-20 cm, and 20-40 cm. The average soil N2O emission rate was 8.1 µg N2O-N h-1 m-2 in plots without SS application (control). The application of SS significantly increased the soil N2O emissions by 7-10 times as to control. The increased N2O emissions were positively related to the soil total phosphorus and nitrogen and negatively correlated with copper and zinc, which increased with the SS application. However, the potential ecological risk index (Ei) and the comprehensive potential ecological risk index (RI) of PTEs were lower than 40 and 150 respectively, which indicating a low toxicity of PTEs to soil health. After seven months of SS application, the priming effects of SS on soil N2O emissions gradually diminished. These findings suggest that the application of SS may increase N2O emissions at the initial stages of application (<7 months) and may have a low PTEs pollution risk, even at a high SS addition rate (4.5 kg m-2).
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Eucalyptus , Metais Pesados , Solo/química , Esgotos , Nitrogênio/análise , Fertilizantes/análise , Óxido Nitroso/análise , Agricultura , ChinaRESUMO
The aim of this study is to investigate and analyze the effect of different application sequences of CO2 fractional laser and triamcinolone acetonide injection on the application effect of hypertrophic scar in one operation. Patients with hypertrophic scars who received CO2 lattice laser combined with triamcinolone acetonide injection from January 2021 to December 2022 were retrospectively analyzed. According to the different initial operations, they were divided into CO2 FL-TA group and TA-CO2 FL group. The Vancouver Scar Scale score and scar thickness of the two groups before and after treatment were analyzed. The complications occurred in the two groups during the treatment period. The clinical efficacy of the two groups before and after the treatment was calculated. Before treatment, there was no difference in scar thickness and VSS score between the two groups (P > 0.05). After treatment, the above indexes in CO2 FL-TA group were significantly better than those in TA-CO2 FL group (P < 0.05); the incidence of adverse reactions in CO2 FL-TA group was 9.38%, which was significantly lower than that in TA-CO2 FL group (18.75%) (P < 0.05); the total effective rate of CO2 FL-TA group was 90.63%, which was significantly higher than that in TA-CO2 FL group (65.63%) (P < 0.05). In the process of combined CO2 fractional laser and triamcinolone acetonide injection in the treatment of hypertrophic scars, CO2 fractional laser treatment first, and then triamcinolone acetonide injection can reduce the number of treatments, reduce the incidence of adverse reactions, and achieve more satisfactory treatment effect.
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Cicatriz Hipertrófica , Lasers de Gás , Humanos , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/radioterapia , Triancinolona Acetonida/uso terapêutico , Dióxido de Carbono/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Lasers de Gás/uso terapêuticoRESUMO
A series of side-chain thioether-linked OEGylated poly(glutamic acid) (PGAs) have been synthesized by "thiol-ene" synthetic methodology, where both the oligo-ethylene glycol (OEG) length and the hydrophobic linkers at the side chains are varied to learn how these structural features affect the secondary structure and thermoresponsive behaviors in water. Before side-chain oxidation, the structural factors affecting the α-helicity include the backbone length, the OEG length, and the hydrophobic linkers' length at the side chains; however, the OEG length plays the most crucial role among these factors because longer OEG around the peripheral side chains can stop water penetration into the backbone to disturb the intramolecular H bonds, which finally allows stabilizing the α-helix; after the oxidation, the polypeptides show increased α-helicity because of the enhanced hydrophilicity. More interestingly, a rare oxidation-induced conformation transition from the ordered ß-sheet to the ordered α-helix can be achieved. In addition, only the OEGylated poly(glutamic acids) (PGAs) with shorter hydrophobic linkers and longer OEG can display the thermoresponsive properties before the oxidation but the subsequent oxidation can cause the polypeptides bearing longer hydrophobic linkers to exhibit the thermosensitivity since sulfone formation at the side chain can lead to final hydrophilicity-hydrophobicity balance. This work is meaningful to understand the secondary structure-associated solution behaviors of the synthetic polypeptides.
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BACKGROUND: Delayed neurocognitive recovery after surgery is associated with poor outcome. Most surgeries require general anesthesia, of which sevoflurane and propofol are the most commonly used inhalational and intravenous anesthetics. The authors tested the primary hypothesis that patients with laparoscopic abdominal surgery under propofol-based anesthesia have a lower incidence of delayed neurocognitive recovery than patients under sevoflurane-based anesthesia. A second hypothesis is that there were blood biomarkers for predicting delayed neurocognitive recovery to occur. METHODS: A randomized, double-blind, parallel, controlled study was performed at four hospitals in China. Elderly patients (60 yr and older) undergoing laparoscopic abdominal surgery that was likely longer than 2 h were randomized to a propofol- or sevoflurane-based regimen to maintain general anesthesia. A minimum of 221 patients was planned for each group to detect a one-third decrease in delayed neurocognitive recovery incidence in propofol group compared with sevoflurane group. The primary outcome was delayed neurocognitive recovery incidence 5 to 7 days after surgery. RESULTS: A total of 544 patients were enrolled, with 272 patients in each group. Of these patients, 226 in the propofol group and 221 in the sevoflurane group completed the needed neuropsychological tests for diagnosing delayed neurocognitive recovery, and 46 (20.8%) in the sevoflurane group and 38 (16.8%) in the propofol group met the criteria for delayed neurocognitive recovery (odds ratio, 0.77; 95% CI, 0.48 to 1.24; P = 0.279). A high blood interleukin-6 concentration at 1 h after skin incision was associated with an increased likelihood of delayed neurocognitive recovery (odds ratio, 1.04; 95% CI, 1.01 to 1.07; P = 0.007). Adverse event incidences were similar in both groups. CONCLUSIONS: Anesthetic choice between propofol and sevoflurane did not appear to affect the incidence of delayed neurocognitive recovery 5 to 7 days after laparoscopic abdominal surgery. A high blood interleukin-6 concentration after surgical incision may be an independent risk factor for delayed neurocognitive recovery.
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Abdome/cirurgia , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Complicações Cognitivas Pós-Operatórias/epidemiologia , Propofol/efeitos adversos , Sevoflurano/efeitos adversos , Idoso , Anestésicos Inalatórios/sangue , Anestésicos Intravenosos/sangue , Biomarcadores/sangue , China/epidemiologia , Método Duplo-Cego , Feminino , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Complicações Cognitivas Pós-Operatórias/sangue , Propofol/sangue , Sevoflurano/sangueRESUMO
Cephalotaxus oliveri is a tertiary relict conifer endemic to China, regarded as a national second-level protected plant in China. This species has experienced severe changes in temperature and precipitation in the past millions of years, adapting well to harsh environments. In view of global climate change and its endangered conditions, it is crucial to study how it responds to changes in temperature and precipitation for its conservation work. In this study, single-molecule real-time (SMRT) sequencing and Illumina RNA sequencing were combined to generate the complete transcriptome of C. oliveri. Using the RNA-seq data to correct the SMRT sequencing data, the four tissues obtained 63,831 (root), 58,108 (stem), 33,013 (leaf) and 62,436 (male cone) full-length unigenes, with a N50 length of 2523, 3480, 3181, and 3267 bp, respectively. Additionally, 35,887, 11,306, 36,422, and 25,439 SSRs were detected for the male cone, leaf, root, and stem, respectively. The number of long non-coding RNAs predicted from the root was the largest (11,113), and the other tissues were 3408 (stem), 3193 (leaf), and 3107 (male cone), respectively. Functional annotation and enrichment analysis of tissue-specific expressed genes revealed the special roles in response to environmental stress and adaptability in the different four tissues. We also characterized the gene families and pathways related to abiotic factors. This work provides a comprehensive transcriptome resource for C. oliveri, and this resource will facilitate further studies on the functional genomics and adaptive evolution of C. oliveri.
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Cephalotaxus/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Transcriptoma/genética , Sistema Enzimático do Citocromo P-450/classificação , Sistema Enzimático do Citocromo P-450/genética , Ontologia Genética , Anotação de Sequência Molecular , Especificidade de Órgãos/genética , Filogenia , Folhas de Planta/genética , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Raízes de Plantas/genética , Caules de Planta/genética , Sementes/genética , Análise de Sequência de RNA/métodosRESUMO
This paper proposes an improved artificial bee colony algorithm named Weighted Global ABC (WGABC) algorithm, which is designed to improve the convergence speed in the search stage of solution search equation. The new method not only considers the effect of global factors on the convergence speed in the search phase, but also provides the expression of global factor weights. Experiment on benchmark functions proved that the algorithm can improve the convergence speed greatly. We arrive at the gas diffusion concentration based on the theory of CFD and then simulate the gas diffusion model with the influence of buildings based on the algorithm. Simulation verified the effectiveness of the WGABC algorithm in improving the convergence speed in optimal deployment scheme of gas sensors. Finally, it is verified that the optimal deployment method based on WGABC algorithm can improve the monitoring efficiency of sensors greatly as compared with the conventional deployment methods.
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Astragalus polysaccharide (APS) derived from A. membranaceus plays a crucial role in traditional Chinese medicine. These polysaccharides have shown antitumor effects and are considered safe. Thus, they have become increasingly important in cancer immunotherapy. APS can limit the spread of cancer by influencing immune cells, promoting cell death, triggering cancer cell autophagy, and impacting the tumor microenvironment. When used in combination with other therapies, APS can enhance treatment outcomes and reduce toxicity and side effects. APS combined with immune checkpoint inhibitors, relay cellular immunotherapy, and cancer vaccines have broadened the application of cancer immunotherapy and enhanced treatment effectiveness. By summarizing the research on APS in cancer immunotherapy over the past two decades, this review elaborates on the anticancer mechanism of APS and its use in cancer immunotherapy and clinical trials. Considering the multiple roles of APS, this review emphasizes the importance of using APS as an adjunct to cancer immunotherapy and compares other polysaccharides with APS. This discussion provides insights into the specific mechanism of action of APS, reveals the molecular targets of APS for developing effective clinical strategies, and highlights the wide application of APS in clinical cancer therapy in the future.
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Effective lineage-specific differentiation is essential to fulfilling the great potentials of human pluripotent stem cells (hPSCs). In this report, we investigate how modulation of medium pH and associated metabolic changes influence mesendoderm differentiation from hPSCs. We show that daily medium pH fluctuations are critical for the heterogeneity of cell fates in the absence of exogenous inducers. Acidic environment alone leads to cardiomyocyte generation without other signaling modulators. In contrast, medium alkalinization is inhibitory to cardiac fate even in the presence of classic cardiac inducers. We then demonstrate that acidic environment suppresses glycolysis to facilitate cardiac differentiation, while alkaline condition promotes glycolysis and diverts the differentiation toward other cell types. We further show that glycolysis inhibition or AMPK activation can rescue cardiac differentiation under alkalinization, and glycolysis inhibition alone can drive cardiac cell fate. This study highlights that pH changes remodel metabolic patterns and modulate signaling pathways to control cell fate.
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The homeostasis of human pluripotent stem cells (hPSCs) requires the signaling balance of extracellular factors. Exogenous regulators from cell culture medium have been widely reported, but little attention has been paid to the autocrine factor from hPSCs themselves. In this report, we demonstrate that extracellular signal-related kinase 5 (ERK5) regulates endogenous autocrine factors essential for pluripotency and differentiation. ERK5 inhibition leads to erroneous cell fate specification in all lineages even under lineage-specific induction. hPSCs can self-renew under ERK5 inhibition in the presence of fibroblast growth factor 2 (FGF2) and transforming growth factor ß (TGF-ß), although NANOG expression is partially suppressed. Further analysis demonstrates that ERK5 promotes the expression of autocrine factors such as NODAL, FGF8, and WNT3. The addition of NODAL protein rescues NANOG expression and differentiation phenotypes under ERK5 inhibition. We demonstrate that constitutively active ERK5 pathway allows self-renewal even without essential growth factors FGF2 and TGF-ß. This study highlights the essential contribution of autocrine pathways to proper maintenance and differentiation.
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In this study, the effect of hydrothermal treatment with different temperatures (120-180⯰C) on the rheological properties of xanthan gum was evaluated. When the temperature of hydrothermal treatment was relatively low (120⯰C), the rheological properties of the hydrothermally treated xanthan gum was similar to the untreated xanthan gum (pseudoplastic and solid-like/gel-like behavior). However, as the temperature of hydrothermal treatment was higher, the rheological properties of the hydrothermally treated xanthan gum changed greatly (e.g., a wider range of Newtonian plateaus in flow curves, existence of a critical frequency between the storage modulus (G') and the loss modulus (G") in the dynamic viscoelasticity measurement, variation of complex viscosity). Although the hydrothermal treatment showed little influence on the functional groups of xanthan gum, it altered the micromorphology of xanthan gum from uneven and rough lump-like to thinner and smoother flake-like. In addition, higher concentration (2â¯%) of hydrothermally treated xanthan gum made its viscosity close to that of the untreated xanthan gum (1â¯%). Besides, hydrothermal treatment also affected the effect of temperature and salt (CaCl2) adding on the rheological properties of xanthan gum. Overall, this study can provide some useful information on the rheological properties of xanthan gum after hydrothermal treatment.
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Polissacarídeos Bacterianos , Reologia , Temperatura , Polissacarídeos Bacterianos/química , Viscosidade , Água/químicaRESUMO
Herein, we developed a synthetic strategy for the direct construction of C-S bonds to obtain biologically active sulfur-containing compounds and a methodology involving the reductive sulfuration of aldehydes or ketones to obtain diverse substituted thiol, disulfide, and thioester derivatives. EtOCS2K is demonstrated as a potential substitute for the Berzelius reagent or Lawesson's reagent for the construction of C-S bonds.
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Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract (NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive (Calb1+) NTS neurons that are molecularly distinct from Tac1+ neurons. These Calb1+ neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+ NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.
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Anesthesia and surgery activate matrix metalloproteinase 9 (MMP9), leading to blood-brain barrier (BBB) disruption and postoperative delirium (POD)-like behavior, especially in the elderly. Aged mice received intraperitoneal injections of either the MMP9 inhibitor SB-3CT, melatonin, or solvent, and underwent laparotomy under 3 % sevoflurane anesthesia(anesthesia/surgery). Behavioral tests were performed 24 h pre- and post-operatively. Serum and cortical tissue levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured using ELISA. Levels of PDGFRß, MMP9, tight junction, Mfsd2a, caveolin-1, synaptophysin, and postsynaptic densin (PSD)-95 proteins in the prefrontal cortex were assayed using Western blotting. BBB permeability was assessed by detecting IgG in the prefrontal cortex and serum S100ß levels. Anesthesia/surgery-induced peripheral inflammation activated MMP9, which in turn injured pericytes and tight junctions and increased transcytosis, thereby disrupting the BBB. Impaired BBB allowed the migration of peripheral inflammation into the central nervous system (CNS), thereby inducing neuroinflammation, synaptic dysfunction, and POD-like behaviors. However, MMP9 inhibition reduced pericyte and tight junction injury and transcytosis, thereby preserving BBB function and preventing the migration of peripheral inflammation into the CNS, thus attenuating synaptic dysfunction and POD-like behavior. In addition, to further validate the above findings, we showed that melatonin exerted similar effects through inhibition of MMP9. The present study shows that after anesthesia/surgery, inflammatory cytokines upregulation is involved in regulating BBB permeability in aged mice through activation of MMP9, suggesting that MMP9 may be a potential target for the prevention of POD.
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Barreira Hematoencefálica , Metaloproteinase 9 da Matriz , Melatonina , Doenças Neuroinflamatórias , Sevoflurano , Animais , Metaloproteinase 9 da Matriz/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Masculino , Camundongos , Sevoflurano/farmacologia , Doenças Neuroinflamatórias/imunologia , Melatonina/farmacologia , Envelhecimento , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Citocinas/metabolismo , Complicações Pós-Operatórias , Anestesia , Comportamento Animal/efeitos dos fármacos , Laparotomia/efeitos adversos , Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Compostos Heterocíclicos com 1 Anel , SulfonasRESUMO
Unlike megabats, which rely on well-developed vision, microbats use ultrasonic echolocation to navigate and locate prey. To study ultrasound perception, here we compared the auditory cortices of microbats and megabats by constructing reference genomes and single-nucleus atlases for four species. We found that parvalbumin (PV)+ neurons exhibited evident cross-species differences and could respond to ultrasound signals, whereas their silencing severely affected ultrasound perception in the mouse auditory cortex. Moreover, megabat PV+ neurons expressed low levels of complexins (CPLX1-CPLX4), which can facilitate neurotransmitter release, while microbat PV+ neurons highly expressed CPLX1, which improves neurotransmission efficiency. Further perturbation of Cplx1 in PV+ neurons impaired ultrasound perception in the mouse auditory cortex. In addition, CPLX1 functioned in other parts of the auditory pathway in microbats but not megabats and exhibited convergent evolution between echolocating microbats and whales. Altogether, we conclude that CPLX1 expression throughout the entire auditory pathway can enhance mammalian ultrasound neurotransmission.
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Córtex Auditivo , Vias Auditivas , Proteínas do Tecido Nervoso , Transmissão Sináptica , Animais , Masculino , Camundongos , Córtex Auditivo/metabolismo , Vias Auditivas/metabolismo , Ecolocação , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Parvalbuminas/metabolismo , Parvalbuminas/genéticaRESUMO
OBJECTIVE: To investigate the effect of sodium bicarbonated Ringer's solution (BRS) on lactate metabolism, acid-base balance, and clinical outcomes in elderly patients undergoing gastrointestinal surgery. METHODS: A total of 60 elderly patients undergoing gastrointestinal surgery were enrolled in this prospective, randomized controlled study. The participants were randomly assigned to the BRS group (n = 30) or sodium lactated Ringer's solution (LRS) group (n = 30) where they received goal-directed fluid therapy with BRS or LRS, respectively. The primary outcome was the incidence of postoperative hyperlactatemia, whereas the secondary outcomes included pH, bicarbonate, base excess (BE), liver function, and postoperative complications within 30 days. Linear regression was conducted to screen the factors affecting lactate concentration. RESULTS: After fluid therapy, the probability of hyperlactatemia was lower in the BRS group than in the LRS group (3.3% vs. 40.0%, P < 0.001). No significant difference in bicarbonate, pH, and BE was observed between the groups (P > 0.05). Furthermore, the incidence of major complications and the length of hospital stay were not significantly different (P > 0.05). However, the BRS group had a lower risk of minor complications than the LRS group (50.0% vs. 76.7%, P = 0.032), particularly in terms of impaired liver function (16.7% vs. 43.3%, P = 0.024). Diabetes, hypotension, and volume of LRS infused were highly correlated with lactate concentration. CONCLUSION: BRS is more beneficial to the reduction of the incidence of postoperative hyperlactatemia and the risk of minor postoperative complications in elderly patients undergoing gastrointestinal surgery. Therefore, BRS may be a better option for perioperative fluid therapy in elderly patients undergoing gastrointestinal surgery.